Vascular Function in Healthy VolunteersDISCONCT01060930
Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output
A study testing Intravenous infusion of L-NMMA and Nor-epinephrine in people with Vascular Function in Healthy Volunteers, run by University of Edinburgh at 1 site in Sweden.
Trial summary
Exposure to combustion-derived fine particulate air pollution is associated with cardiovascular mortality and morbidity. In previous studies, exposure to diesel exhaust (a major constituent of urban particulate air pollution) has been shown to impair two important functions of the vascular endothelium: vascular… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Vascular Function in Healthy Volunteers
- What is being tested?
- Intravenous infusion of L-NMMA and Nor-epinephrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteSweden
- Study dates
- Mar 2010to Jun 2010
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy volunteers
- Non smokers
- No regular medication (except oral contraceptive)
- No recent respiratory tract infection (within 6 weeks)
Who cannot join
- History of asthma or respiratory disease
- Smoking history
- Pregnancy (positive urinary pregnancy test)
Trial locations and contacts
1 site in 1 country.
About this study
Exposure to combustion-derived fine particulate air pollution is associated with cardiovascular mortality and morbidity. In previous studies, exposure to diesel exhaust (a major constituent of urban particulate air pollution) has been shown to impair two important functions of the vascular endothelium: vascular vasomotor function and endogenous fibrinolysis. Our subsequent studies suggest this impairment of vascular function is mediated by a reduction in nitric oxide bioavailability. In this study we aim to investigate the cardiovascular responses to systemic nitric oxide synthase inhibition following exposure to dilute diesel exhaust.
- Conditions
- Vascular Function in Healthy Volunteers
- Being tested
- Intravenous infusion of L-NMMA and Nor-epinephrine
- Keywords
- Nitric oxide, Diesel exhaust, Air pollution, Cardiac output, Healthy volunteers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous infusion of L-NMMA and Nor-epinephrineDrug
Also called L-NMMA: Clinalfa Basic, Bachem, Germany
Intravenous infusion of 3mg/kg L-NMMA (L-NG-monomethyl arginine; NO synthase inhibitor) and nor-epinephrine at 50 ng/kg/min. Each infusion to run over 15 mins and separated by 45 min to allow return to baseline. Drugs infused in a randomised order. During the study, blood pressure will be measured invasively using an intra-arterial radial artery cannula, central arterial stiffness measured using peripheral arterial tonometry and cardiac output using thoracic bioimpedance.
| Study group | Role | What they receive |
|---|---|---|
| Diesel exhaust exposure | Experimental | 1 hour exposure to dilute diesel exhaust ~ 300 mcg/m3 - during intermittent exercise Receives: Drug: Intravenous infusion of L-NMMA and Nor-epinephrine |
| Air exposure | Experimental | 1 hour exposure to filtered air during intermittent exercise Receives: Drug: Intravenous infusion of L-NMMA and Nor-epinephrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood pressure response to NO inhibition
Measured: Blood pressure will be measured continuously through the vascular study using intra-arterial monitoring
Secondary outcomes (6)
Heart rate response to systemic nitric oxide inhibition
Measured: Heart rate will be measured continuously throughout the study period using continous electrocardiography
Central arterial stiffness following NO inhibition
Measured: Measured at baseline, and every 5 minutes during the 2-hour vascular study
Cardiac output during NO inhibition
Measured: Measured at baseline, and every 5 minutes during the 2-hour vascular study
Plasma nitrite (NO) concentrations
Measured: Measured at baseline, and every 15 minutes during the 2-hour vascular study
Platelet activation and platelet-monocyte binding
Measured: Measured at baseline, and every 30 minutes during the 2-hour vascular study
Heart rate variability
Measured: Heart rate will be measured continuously throughout the study period using continous electrocardiography, and HRV subsequently determined for the whole study period and the 2-hour vascular study separately
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2010 (estimated)
- Study startMar 2010
- Primary completionJun 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Vascular Function in Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian, Umeå University
- Responsible party
- Sponsor
- Investigators
- Jeremy P Langrish, MB BCh MRCP, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01060930
- Sponsor's protocol ID
- DISCO
- Acronym
- DISCO
- Status last verified
- Apr 2011
- First submitted
- 28 Jan 2010
- Last updated
- 16 Dec 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Langrish JP, Unosson J, Bosson J, Barath S, Muala A, Blackwell S, Soderberg S, Pourazar J, Megson IL, Treweeke A, Sandstrom T, Newby DE, Blomberg A, Mills NL. Altered nitric oxide bioavailability contributes to diesel exhaust inhalation-induced cardiovascular dysfunction in man. J Am Heart Assoc. 2013 Feb 19;2(1):e004309. doi: 10.1161/JAHA.112.004309.
PubMed 23525434
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output
- ClinicalTrials.gov ID
- NCT01060930
- Acronym / sponsor ID
- DISCO / DISCO
- Conditions
- Vascular Function in Healthy Volunteers
- Keywords
- Nitric oxide, Diesel exhaust, Air pollution, Cardiac output, Healthy volunteers
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian, Umeå University
- Study start
- Mar 2010
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 2 Feb 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Exposure to combustion-derived fine particulate air pollution is associated with cardiovascular mortality and morbidity. In previous studies, exposure to diesel exhaust (a major constituent of urban particulate air pollution) has been shown to impair two important functions of the vascular endothelium: vascular vasomotor function and endogenous fibrinolysis. Our subsequent studies suggest this impairment of vascular function is mediated by a reduction in nitric oxide bioavailability. In this study we aim to investigate the cardiovascular responses to systemic nitric oxide synthase inhibition following exposure to dilute diesel exhaust.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Diesel exhaust exposure | Experimental | Drug: Intravenous infusion of L-NMMA and Nor-epinephrine1 hour exposure to dilute diesel exhaust ~ 300 mcg/m3 - during intermittent exercise |
| Air exposure | Experimental | Drug: Intravenous infusion of L-NMMA and Nor-epinephrine1 hour exposure to filtered air during intermittent exercise |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Healthy volunteers
- Non smokers
- No regular medication (except oral contraceptive)
- No recent respiratory tract infection (within 6 weeks)
Key exclusion criteria (3 listed)
- History of asthma or respiratory disease
- Smoking history
- Pregnancy (positive urinary pregnancy test)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous infusion of L-NMMA and Nor-epinephrineAlso: L-NMMA: Clinalfa Basic, Bachem, GermanyIntravenous infusion of 3mg/kg L-NMMA (L-NG-monomethyl arginine; NO synthase inhibitor) and nor-epinephrine at 50 ng/kg/min. Each infusion to run over 15 mins and separated by 45 min to allow return to baseline. Drugs infused in a randomised order. During the study, blood pressure will be measured invasively using an intra-arterial radial artery cannula, central arterial stiffness measured using peripheral arterial tonometry and cardiac output using thoracic bioimpedance. | Drug | Air exposure, Diesel exhaust exposure |
Primary outcome
Blood pressure response to NO inhibition
Time frame: Blood pressure will be measured continuously through the vascular study using intra-arterial monitoring
6 secondary outcomes
Heart rate response to systemic nitric oxide inhibition
Time frame: Heart rate will be measured continuously throughout the study period using continous electrocardiography
Central arterial stiffness following NO inhibition
Time frame: Measured at baseline, and every 5 minutes during the 2-hour vascular study
Cardiac output during NO inhibition
Time frame: Measured at baseline, and every 5 minutes during the 2-hour vascular study
Plasma nitrite (NO) concentrations
Time frame: Measured at baseline, and every 15 minutes during the 2-hour vascular study
Platelet activation and platelet-monocyte binding
Time frame: Measured at baseline, and every 30 minutes during the 2-hour vascular study
Heart rate variability
Time frame: Heart rate will be measured continuously throughout the study period using continous electrocardiography, and HRV subsequently determined for the whole study period and the 2-hour vascular study separately
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2011.
- Derived from this study: PubMed 23525434Langrish JP, Unosson J, Bosson J, Barath S, Muala A, Blackwell S, Soderberg S, Pourazar J, Megson IL, Treweeke A, Sandstrom T, Newby DE, Blomberg A, Mills NL. Altered nitric oxide bioavailability contributes to diesel exhaust inhalation-induced cardiovascular dysfunction in man. J Am Heart Assoc. 2013 Feb 19;2(1):e004309. doi: 10.1161/JAHA.112.004309.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeremy P Langrish, MB BCh MRCP principal investigator
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intravenous infusion of L-NMMA and Nor-epinephrine in people with Vascular Function in Healthy Volunteers, run by University of Edinburgh at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Dec 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood pressure response to NO inhibition (time frame: Blood pressure will be measured continuously through the vascular study using intra-arterial monitoring). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01060930, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2011.